title: Effect of prednisone on the pharmacokinetics of the integrase inhibitor dolutegravir.
abstract: Prednisone, a corticosteroid frequently used to treat common AIDS-related illnesses and comorbidities, has been shown to induce drug metabolism. This study was performed to determine whether prednisone coadministration affected the pharmacokinetics of dolutegravir (DTG). In this open-label, repeat-dose study, 12 healthy subjects were administered DTG at 50 mg daily alone for 5 days and then with concomitant prednisone for 10 days (prednisone at 60 mg daily for 5 days, followed by a 5-day taper). Serial blood sampling and safety assessments were performed during the trial. Pharmacokinetic parameters were determined using noncompartmental methods and geometric least-square mean ratios, and 90% confidence intervals were generated. Coadministration of DTG and 5-day high-dose prednisone with a 5-day taper had a modest effect on DTG exposure. The area under the DTG plasma concentration-time curve, maximum observed DTG concentration, and 24-hour postdose DTG concentration were increased by 11%, 6%, and 17%, respectively, on day 10 of the combination. Similar results were observed after 5 days of DTG and prednisone. Dolutegravir and prednisone coadministration was well tolerated. The changes in plasma exposures of DTG in healthy individuals as a result of prednisone dosing were not clinically significant. No dose adjustment is required for DTG coadministered with prednisone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01425099.).
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Ivy H
authors.initials: IH
authors.lastname: Song
authors.forename: Julie
authors.initials: J
authors.lastname: Borland
authors.forename: Shuguang
authors.initials: S
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Savina
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Peppercorn
authors.forename: Stephen
authors.initials: S
authors.lastname: Piscitelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D019428:HIV Integrase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006575:Heterocyclic Compounds, 3-Ring / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D011241:Prednisone / Q000097:blood / Q000494:pharmacology*; D011728:Pyridones; D000099226:Dolutegravir
chemical_list: D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011241:Prednisone; D011728:Pyridones; D000099226:Dolutegravir